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New Developments in Drug Treatment
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Alexander S. Pym, Camus Nimmo, James Millard
Carbapenem β-lactam antibiotics, imipenem, ertapenem and meropenem, in combination with the β-lactamase inhibitor clavulinic acid offer a better alternative. Carbapenems bind high-molecular weight penicillin-binding proteins, inactivating the l,d-transpeptidases that form cell wall crosslinks161 and are less susceptible to BlaC. For example, the MIC for meropenem−clavulinic acid has been reported in a range from 0.32 to 1.28 μg/mL for drug-susceptible reference strains of M. tuberculosis.162,163 There have been some favorable clinical reports with carbapenems164 but the results from mouse studies have been equivocal with the meropenem−clavulinic acid combination.165,166 A fall in bacterial counts in treated mice was only seen in one of the studies where the carbapenem was given at a dose of 300 mg/kg. Recently, the currently available formulation of ceftazidime, an older cephalosporin, in combination with avibactam, a potent inhibitor of BlaC, was identified to have anti-mycobacterial activity in an in vitro screen which was followed by further evaluation in the hollow fiber system. It demonstrated good sterilization of drug-resistant isolates at clinically achievable concentrations and may offer another option where alternatives are limited.167
Surgical infection
Published in Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie, Bailey & Love's Short Practice of Surgery, 2018
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie
Pseudomonas spp. tend to colonise burns and tracheostomy wounds, as well as the urinary tract. Once Pseudomonas has colonised wards and intensive care units, it may be difficult to eradicate. Surveillance of cross-infection is important in outbreaks. Hospital strains become resistant to b-lactamase as resistance can be transferred by plasmids. Wound infections need antibiotic therapy only when there is progressive or spreading infection with systemic signs. The aminoglycosides and the quinolones are effective, but some cephalosporins and penicillin may not be. Many of the carbapenems (e.g. meropenem) are useful in severe infections.
Meropenem and Meropenem–Vaborbactam
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Anton Y. Peleg, Patrick N. A. Harris
The treatment of hospital-acquired or healthcare-associated pneumonia should be based on local microbiologic susceptibility data. Empirical therapy regimens should be institution specific, maximizing the coverage of causative organisms that are likely at a given time in the hospital stay, taking into account the severity of illness and previous antibiotic exposures of the patient. Meropenem is one of several therapeutic options for hospital-acquired or healthcare-associated pneumonia, although reserved for patients at high-risk for multidrug-resistant pathogens (ATS/IDSA, 2005). Two prospective, randomized studies have been performed that demonstrate the efficacy of meropenem (1 g every 8 hours) compared with ceftazidime plus an aminoglycoside (Sieger et al., 1997; Alvarez Lerma and Serious Infection Study Group, 2001), both showing a slight but significant benefit with meropenem (Table 38.10). Given the difficulties of diagnosing ventilator-associated pneumonia and the broad-spectrum nature of meropenem, it is important to reevaluate the patient at 48–72 hours to assess the clinical status and microbiologic data. Deescalation to a more narrow-spectrum, microbiologically guided therapy is ideal if possible.
Therapeutic drug monitoring-guided dosing for pediatric cystic fibrosis patients: recent advances and future outlooks
Published in Expert Review of Clinical Pharmacology, 2023
Siân Bentley, Jamie Cheong, Nikesh Gudka, Sukeshi Makhecha, Simone Hadjisymeou-Andreou, Joseph F Standing
PK studies have shown that clearance of both ceftazidime and meropenem is higher in children with CF compared to those without, therefore higher or more frequent dosing is required [36–38]. Ceftazidime intermittent 30-min infusions achieve a T>MIC 60–70% in children with CF if Pseudomonas aeruginosa MIC <8 mg/L using higher doses of ≥50 mg/kg TDS, compared to non-CF children who can attain this target when MIC are ≤16 mg/L [36]. To reach the recommended T>MIC (65%) for ceftazidime and meropenem (40%), short intermittent infusions need to be changed to 3-h extended infusions when MIC ≥ 8mcg/L for ceftazidime [36] or MIC ≥4 mg/ml for meropenem [37]. Conversely, the use of ceftazidime as a continuous infusion achieves the PK/PD target for all children, with and without CF, even at MIC 16 mg/L [36]. Of note beta-lactam clearance (ceftazidime, meropenem, aztreonam, piperacillin/tazobactam, and ticarcillin/clavulanate) has also been shown to increase between Days 2 and 7 in adults with CF receiving continuous infusions, necessitating a 20% increase in beta-lactam dose in approximately 50% of patients [39].
A rare complication of laparoscopic Roux-en-Y gastric bypass: case report of gastric remnant necrosis
Published in Acta Chirurgica Belgica, 2023
Astrid Rycx, Hendrik Maes, Yves Van Nieuwenhove
The intravenous antibiotics were continued and after twelve days, the patient could be transferred to the gastro-intestinal surgery ward. There, she had a sudden rise of CRP (260 mg/L) with again tachycardia and fever. CT abdomen showed no fluid collections and blood and sputum cultures were negative. Faeces culture was positive for Klebsiella, Pseudomonas and E. Coli, which led to a switch in antibiotics. Meropenem was started and after three days, an improvement of the symptoms and laboratory results was seen. After two weeks at the gastro-intestinal surgery ward, the patient was able to leave the hospital in a good condition. At the follow-up appointment after hospital discharge, the patient complained about persistent dysphagia and nausea. She did not report pain and she had lost five kilograms since her hospital discharge.
Meropenem/vaborbactam: a next generation β-lactam β-lactamase inhibitor combination
Published in Expert Review of Anti-infective Therapy, 2020
Andrea Novelli, Paola Del Giacomo, Gian Maria Rossolini, Mario Tumbarello
Meropenem has been widely used in pediatric infections, however, since at present M/V has been registered only in adults, there are no published dosing recommendations for the use of M/V in this setting and the results of the TANGOKIDS, a dose-finding pharmacokinetic study in children with serious bacterial infections, are not yet available. At present, there is only a reference related to a case report on a 4-year-old male child with a central line for chronic total parenteral nutrition and hydration management and a KPC-producing K. pneumoniae bloodstream infection (BSI), successfully treated with M/V at a dosage of 40 mg/kg every 6 hours infused over 3 hours. Meropenem peak serum concentrations obtained on day 5 were 51.3 mg/L and the Authors adapted the optimized meropenem treatment schedule obtained in a previous PK-PD study in critically ill children in order to achieve a probability of target attainment (PTA) of 40% fT > MIC [67,68].